125I-insulin binds to IM-9 cells (human) and hepatocytes (rat). By using quantitative EM autoradiography as a probe, it can be shown that labeled insulin is internalized by a process which appears to be time- and temperature-dependent. Studies indicate that the microvillus surface is involved in initial hormone binding and the receptors are lost from this surface in a time- and temperature-dependent manner. Other labeled proteins (low density lipoprotein, epidermal growth factor, human growth hormone, glucagon, and anti-insulin receptor antibody) appear to behave in the same fashion i.e. initial binding followed by internalization.